Ceftolozane/tazobactam for the treatment of bacteremia: a systematic literature review (SLR)

Background: Bloodstream infections (BSIs), or bacteremia, are responsible for considerable disease burden. Increasing rates of antibiotic resistance and delays in selection of appropriate treatment lead to increased morbidity, mortality, and costs. Due to limitations of current standard treatments, especially for bacteremia caused by resistant pathogens, a systematic literature review (SLR) was conducted to understand the utilization of ceftolozane/tazobactam (UT) in bacteremia. Methods: Electronic database searches of EMBASE (R), MEDLINE (R), CCTR and Northern Lights, as well as hand searches of conference proceedings from the last two annual meetings (i.e., 2018, 2019) of the European Congress of Clinical Microbiological and Infectious Diseases (ECCMID) and the Infectious Diseases Society of America's annual meeting (IDWeek) were conducted. A total of 23 studies reporting on patients with bacteremia receiving UT were included in the review. Results: Most studies were observational (k=20 studies), though few interventional studies were also identified (k= 3). Heterogeneity was ubiquitous with respect to source of bacteremia (i.e., primary or secondary), source of infection (for secondary bacteremia), pathogen type, antibiotic resistance, C/T dose, and outcome definitions. This heterogeneity, along with limited data, and small sample sizes (n =1 to 31) made it difficult to draw any substantial conclusions, though overall results were favorable to C/T with respect to the outcomes of interest. Nineteen studies reported clinical cure or success (primary bacteremia: k= 6, reported range: 33.3% to 100%; secondary bacteremia: k= 8, 60% to 100%; mixed/unspecified bacteremia: k= 10, 50% to 91.7%). Eight studies reported microbiological cure or eradication rates (primary: k= 3, all reporting 100%; secondary: k=4, 68% to 80%; mixed/unspecified: k= 5, 60% to 80%). Thirteen studies reported mortality (primary: k=4, 0% to 14%; secondary: k = 7, 0% to 100%; or mixed/unspecified bacteremia: k=7, 0% to 51.6%). One study each also reported composite clinical response, relapse, hospital re-admission, and hospital length of stay. Conclusions: Although the available evidence and observed trends for C/T in bacteremia should be interpreted with caution, the direction of effect would support the utilization of C/T for these difficult to treat infections. Future research should supplement the existing evidence by considering the impact of key treatment effect modifiers without contributing to the observed heterogeneity.